As parts of collaborative studies with other research groups, Laboratory of Biophysics synthesizes large quantities of oligonucleotides (DNA and RNA) and their analogs. During the time period covered by this summary several oligonucleotide phosphorothioates, either unlabeled, containing 5-bromodeoxyuridine marker (for detection with specific antibodies) or labeled with radioactive sulfur-35 isotope were synthesized and purified.The compounds are currently tested in Prof. Cheng's laboratory for their cellular uptake and distribution. The study is expected to provide information important in designing better antisense agents. The second part of the project is a continuation of our Laboratory previous collaboration with Dr. Tom James at the University of California in San Francisco. The goal of this project is to study an application of 15N NMR for RNA structure determination. As a model compound, 2'-O-methylated RNA/DNA hybrid oligonucleotide was synthesized and characterized. The compound is currently studied by Dr. Weisz. When the preliminary structural assignments are completed a nitrogen-15 labeled ribonucleotide analog will be synthesized in our Laboratory.